Acute Ischemic Stroke (AIS) is conventionally treated mainly by thrombolysis or neuroprotection. Neuroprotection refers to medicament or measures, during treatment of AIS, that are able to inhibit pathological and biochemical reactions of brain tissue caused by ischemia, interfere with various pathways of ischemic cascade and prolong survival of neurons.
Neuroprotection has currently become one of the research hotspots in the field of AIS treatment. Various neuroprotectants are under clinical development, the mechanism of which is to prevent or limit brain damage resulted from ischemia by blocking various harmful pathological processes due to ischemia, so as to reduce brain tissue death and promote function recovery. The neuroprotectants can reduce cerebral infarct size; do not result in hemorrhage complication that may occur during thrombolytics or anticoagulants therapy; and can be used without confirmation of etiology, making early treatment possible. The therapeutic effect of neuroprotectants is therefore promising.
There is no neuroprotectant yet, however, that has been proven safe and effective. Drugs that are under clinical trials and have potential value of clinical application include calcium channel blockers (CCB), calcium channel modulators, glutamate release inhibitors, γ-aminobutyric acid (GABA) receptor agonists, free radical scavengers, anti-intercellular adhesion molecule antibodies, and so on.
Among various compounds, neuroactive steroids draw growing concern due to their comprehensive effect in neuroprotection. The levels of neuroactive steroids are correlated with the development and progression of some central nervous system (CNS) diseases, and play a significant role in modulating neuron damage, death, and those CNS diseases. These steroid hormones, either natural or synthetic with activity in nerve tissues, were named neuroactive steroids (NAS) since 1980s. These steroid hormones have been used clinically as replacement therapy. Estrogen is known to be one of the NAS that have the strongest neuroprotective effect. The ovaries of menopausal women do not produce estrogen again, probably leading to beta-amyloid protein (Aβ) deposition and then Alzheimer's disease (AD). Administration of estrogen can significantly reduce the levels of Aβ in brain. Clinically, estrogen treatment of AD has achieved good results. It was demonstrated that allopregnanolone protects cultured hippocampal neurons in vitro against irreversible neurotoxic insult by hypoxia or glutamate. 5α-androstane-3β,5,6β-triol (YC-6) is a compound, found having neuroprotective effect during our research on neurosteroids, with the following structural formula. Information retrieval until now did not reveal any reports about pharmacological effect of YC-6 or its neuroactivity/neuroprotective effect.
